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What is the Optimal Sequence of Discontinuation for vasopressors in Septic Shock?

Updated: Apr 15, 2023

What is the Optimal Sequence of Discontinuation for vasopressors in Septic Shock?

Septic shock is a life-threatening condition that requires timely and effective treatment to improve patient outcomes. Vasopressors, including norepinephrine and vasopressin, play a crucial role in the management of septic shock. However, there is limited guidance on the optimal sequence of discontinuation for these vasopressors. This article will discuss the findings from three retrospective studies examining the effects of discontinuing norepinephrine and vasopressin in different sequences on patient outcomes, including hypotension, hemodynamic instability, and mortality.

So, before we present the available evidence, let try to answer this question:

What is your approach to weaning vasopressors?

  • Wean norepinephrine first

  • Wean vasopressin first

  • It does not matter!

The Evidence on Vasopressors Weaning Sequence in Septic Shock

Hammond et al in a retrospective cohort study investigated the discontinuation of norepinephrine and vasopressin in the recovery phase of septic shock in critically ill patients from May 2014 to June 2016. The study aimed to determine the effects of discontinuation order on clinically significant hypotension. Results showed that when vasopressin was discontinued first, there was a higher occurrence of clinically significant hypotension (67.8% vs. 10.9%, P < .001). However, there were no differences in intensive care unit or hospital stay duration. The study concluded that adult patients in the resolving phase of septic shock may be less likely to develop clinically significant hypotension if vasopressin is the final vasopressor discontinued [1].

Bissell et al in another retrospective study evaluated the optimal sequence for discontinuing vasopressin therapy in septic shock patients who received concurrent norepinephrine and vasopressin for vasoactive support. Of the 152 patients initially considered, 61 patients were included in the analysis. The primary outcome was hemodynamic instability, which included factors such as hypotension after vasopressor discontinuation, fluid bolus administration, increased norepinephrine requirements, or addition of an alternative vasopressor. The study found that discontinuing vasopressin before norepinephrine was associated with a significant increase in hemodynamic instability (74% vs 16.7%, P < .01) and a shorter time to hemodynamic instability (5 vs 15 hours, P < .01). The conclusion suggests that vasopressin discontinuation prior to stopping norepinephrine infusion may result in an increased risk of hemodynamic instability [2].

A third retrospective study aimed to determine the incidence of hypotension within 24 hours of discontinuing norepinephrine (NE) or vasopressin (VP) first in septic shock patients receiving both vasopressors. A total of 80 patients admitted to the medical and surgical intensive care units were included. The results showed that hypotension within 24 hours of the first agent discontinuation (DC) was higher in the VP DC first group (62.2% vs. 28.6%, P=0.004), while hospital length of stay and ICU mortality were similar in both groups. Multivariate analysis identified VP DC first as an independent predictor of hypotension (odds ratio = 7.2; CI = 2.3-22.7). The study concluded that discontinuing VP first in septic shock patients on concomitant NE and VP was associated with an increased incidence of hypotension, suggesting the need for future prospective control trials [3].

And now let as the question again and see if you were influenced with these retrospective studies:

What is your approach to Weaning Vasopressors in septic shock?

  • Wean norepinephrine first

  • Wean vasopressin first

  • It does not matter!


The findings from these three retrospective studies suggest that discontinuing vasopressin before norepinephrine in septic shock patients may be associated with an increased risk of hypotension and hemodynamic instability. Although there were no significant differences in mortality or hospital length of stay, the higher incidence of hypotension warrants further investigation. Future prospective control trials are needed to better understand the implications of vasopressor discontinuation sequences and to establish evidence-based guidelines for clinicians managing septic shock patients.


  1. Hammond DA, McCain K, Painter JT, Clem OA, Cullen J, Brotherton AL, Chopra D, Meena N. Discontinuation of Vasopressin Before Norepinephrine in the Recovery Phase of Septic Shock. J Intensive Care Med. 2019 Oct;34(10):805-810. doi: 10.1177/0885066617714209. Epub 2017 Jun 15. PMID: 28618919.

  2. Bissell BD, Magee C, Moran P, Bastin MLT, Flannery AH. Hemodynamic Instability Secondary to Vasopressin Withdrawal in Septic Shock. J Intensive Care Med. 2019 Sep;34(9):761-765. doi: 10.1177/0885066617716396. Epub 2017 Jul 28. PMID: 28750598.

  3. Musallam N, Altshuler D, Merchan C, Zakhary B, Aberle C, Papadopoulos J. Evaluating Vasopressor Discontinuation Strategies in Patients With Septic Shock on Concomitant Norepinephrine and Vasopressin Infusions. Ann Pharmacother. 2018 Aug;52(8):733-739. doi: 10.1177/1060028018765187. Epub 2018 Mar 21. PMID: 29560736.

1,093 views2 comments

2 comentários

Amazing as usual

Thank for the clear summary

What about the cost effectiveness, since vasopressin is much more expensive compare to norepinephrine? We diffentily need further prospective study to evaluate the outcome of mortality and morbidity end organ damage, short and long term outcome

Thanks again for the summary

Mazen Kherallah
Mazen Kherallah
08 de abr. de 2023
Respondendo a

I think if benefits on patient-centered outcomes are confirmed by a well-designed RCT, then cost effectiveness study would be needed.

What we did at Sanford is to give a fixed 0.03 dose instead of 0.04.

I came across this initiative for cost saving:

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